This report describes the case of a woman in her late forties with a history of large uterine fibroids who presented to the Emergency Department with colicky suprapubic pain and urinary symptoms. Initial computed tomography (CT) showed uncomplicated acute diverticulitis but despite antibiotic treatment, her condition worsened, and a follow-up CT revealed sigmoid perforation, requiring high anterior resection and subtotal hysterectomy. The case highlights how large fibroids exert external pressure on the colon, impairing motility and increasing the risk of diverticula formation. Alterations in the gut microbiome may contribute to colonic mucosal inflammation, commonly seen in diverticular disease. Patients with uterine fibroids have altered microbiome composition, which could further increase the risk of diverticular disease. These findings provide a pathway for future research into the influence of uterine fibroids on the pathophysiology of diverticular disease.